ACIVICIN, a fermentation product of Streptomyces sviceus is an amino acid anti-cancer agent. ACIVICIN and the microbiological process for producing it are claimed in U.S. Pat. Nos. 3,856,807 and 3,878,047. A complete chemical synthesis of it is described in U.S. Pat. No. Re. 31,578. In humans it causes reversible, dose-limiting CNS effects such as sedation, ataxia, personality changes and hallucinations. These effects limit the maximum dose of acivicin in cancer patients.
In the cat, a species that exhibits some of the acivicin-induced CNS symptoms experienced by humans, it has been shown that an infusion of Aminosyn, 10%.RTM. (a mixture of 16 amino acids), prior and subsequent to i.p. treatment with acivicin, prevented symptoms of drug-induced CNS toxicity and lowered the brain levels of acivicin to 15%-20% of controls, effects presumably due to blockage of drug-uptake into the brain by the increased plasma levels of amino acids. Aminosyn infusion also increased the total clearance of acivicin by ca. two-fold, resulting in lower drug levels in other tissues but not to the extent occurring in brain. Aminosyn administration did not block the anti-tumor efficacy of acivicin in mice bearing either L1210 leukemia or MX-1 human mammary carcinoma xenografts.
Infusion of an amino acid solution composed of alanine, arginine, histidine, proline, serine, typrosine and glycine (none of which are large neutral amino acids) was ineffective at preventing acivicin-induced CNS toxicity in the cat.